Abstract

Neutrophils are often considered being just cells of the first line defense against pathogens. They are endowed with an arsenal of deadly weapons like reactive oxygen species, proteases and anti-microbial peptides. In a cellular process referred to as degranulation neutrophils secrete preformed chemokines and cytokine that recruit and activate further neutrophils as well as other leukocytes. Neutrophils are phagocytes that vigorously ingest and kill bacteria. In addition, they take up several kinds of particular matter including monosodium urate crystals. After strong activation neutrophils eject their chromatin to form pro-inflammatory, chemo-attractive and bactericidal extracellular traps (NETs). These immobilize and kill pathogens and attract further leukocytes. IL8 secretion, neutrophil attraction and NETosis form a self-stimulating feed back loop that initiates and perpetuates inflammation. Important questions are (Q1) How is this potential dangerous vicious circle controlled? (Q2) Which mechanisms are responsible for the resolution of inflammation?

When the density of the neutrophils reaches a certain threshold the NETs tend to aggregate (aggNET) and form extended clumps of chromatin that are decorated with proteolytically active serine proteases. The clumps and the proteases sequester and proteolytically inactivate the neutrophil-derived cytokines and chemokines. Thus NETosis and aggNET formation play important roles for the initiation and resolution of neutrophil-driven inflammation, respectively.

Christine Schauer, Markus Hoffmann, Luis Munoz & Martin Herrmann